1-甲基-1H-吲哚-3-甲酰胺肟 | 390799-61-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 1-甲基-1H-吲哚-3-甲酰胺肟
• 英文名称: 1-methyl-1H-indole-3-carboxamide oxime
• 英文别名: 1-methylindole-3-carboxamide oxime；N'-hydroxy-1-methyl-1H-indole-3-carboximidamide；1-methylindol-3-yl amide oxime；N'-Hydroxy-1-methyl-1H-indole-3-carboxamidine；N'-hydroxy-1-methylindole-3-carboximidamide
• CAS: 390799-61-8
• 化学式: C₁₀H₁₁N₃O
• mdl: MFCD07776713
• 分子量: 189.217
• InChiKey: KGVCOKRDOQOGJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  63.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-甲基-1H-吲哚-3-甲酰胺肟 在 4 A molecular sieve 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 13.83h， 生成 5-<(methylamino)methyl>-3-(1-methyl-1H-indol-3-yl)-1,2,4-oxadiazole trifluoroacetate
  参考文献：
  名称：

  Novel 5-HT3 antagonists. Indole oxadiazoles

  摘要：

  The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3 antagonists are described. The key pharmacophoric elements have been defined as a basic nitrogen, a linking group capable of H-bonding interactions, and an aromatic moiety. The steric limitations of the aromatic binding site have been determined by substitution about the indole ring. Variation of the heterocyclic linking group has shown that while two hydrogen-bonding interactions are possible, only one is essential for high affinity. The environment of the basic nitrogen has been investigated and shown to be optimal when constrained within an azabicyclic system. These results have been incorporated into a proposed binding model for the 5-HT3 antagonist binding site, in which the optimum distance between the aromatic binding site and the basic amine is 8.4-8.9 angstrom and the steric limitations are defined by van der Waals difference mapping.

  DOI：

  10.1021/jm00105a021
• 作为产物：
  描述：

  3-氰基-1-甲基吲哚 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以65%的产率得到1-甲基-1H-吲哚-3-甲酰胺肟
  参考文献：
  名称：

  具有细胞毒活性的新的1,2,4-恶二唑降冰片素衍生物。

  摘要：

  Nortopsentin的新类似物，一种天然的2,4-双（3'-吲哚基）咪唑生物碱，其中天然铅的中心咪唑环被1,2,4-恶二唑部分取代，并且其中7-有效合成了氮杂吲哚部分取代了原来的吲哚部分。在针对HCT-116结肠直肠癌细胞系进行预筛选的所有衍生物中，选择了两种活性最高的化合物，并在不同的人类肿瘤细胞中进行了进一步研究，结果显示其IC50值在微摩尔和亚微摩尔范围内。碘化丙啶染色的MCF-7细胞的流式细胞仪分析表明，两种活性衍生物均导致细胞周期停滞在G0⁻G1期。通过测量磷脂酰丝氨酸对外膜的暴露并使用using啶橙/溴化乙锭双染色观察到的形态学评估，认为由化合物诱导的细胞死亡机制是凋亡的。此外，进一步测试肠正常样分化的Caco-2细胞系，他们表现出对癌细胞的优先毒性。

  DOI：

  10.3390/md17010035

文献信息

• Physiologically active 1,2,4,-oxa- and thiadiazoles
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US04952587A1

  公开（公告）日：1990-08-28

  The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: ##STR2## in which R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, hydroxy(C.sub.1-6)alkyl, halogen, amino, cyano, --CONR.sup.6 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, in which R.sup.6 and R.sup.7 independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylcarbonyl; V represents nitrogen, ##STR3## and W represents oxygen, sulphur or ##STR4## in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: (a) a non-aromatic azacyclic or azabicyclic ring system; or (b) a group of formula --NR.sup.a R.sup.b, in which R.sup.a and R.sup.b independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl or aryl(C.sub.1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供了化合物I的结构或其盐或前药：其中虚线圆圈代表5-成员环中任意位置的一个或两个双键；X、Y和Z独立地代表氧、硫、氮或碳，但至少一个X、Y和Z代表氧、硫或氮；A代表结构II的一个基团：其中R.sup.1代表氢、羟基、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基、C.sub.1-6烷氧基、羟基(C.sub.1-6)烷基、卤素、氨基、氰基、--CONR.sup.6 R.sup.7或--SO.sub.2 NR.sup.6 R.sup.7，其中R.sup.6和R.sup.7独立地代表氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；R.sup.2代表氢、卤素、C.sub.1-6烷基、C.sub.1-6烷氧基或C.sub.1-6烷基羰基；V代表氮，W代表氧、硫或其中R.sup.8代表氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；E代表键或含有1至5个碳原子的直链或支链烷基链，可选地被羟基或苯基取代；F代表：(a)非芳香性氮杂环或氮杂双环系统；或(b)结构--NR.sup.a R.sup.b的一个基团，其中R.sup.a和R.sup.b独立地代表氢、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基或芳基(C.sub.1-6)烷基；这些化合物在治疗精神分裂症（例如精神分裂症和狂躁症）、焦虑、酒精或药物戒断、疼痛、胃排空延缓、胃功能障碍（如消化不良、消化性溃疡、反流性食道炎和胀气）、偏头痛、恶心呕吐以及老年性痴呆症等方面有用。
• A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells
  作者：Camilla Pecoraro、Barbara Parrino、Stella Cascioferro、Adrian Puerta、Amir Avan、Godefridus J. Peters、Patrizia Diana、Elisa Giovannetti、Daniela Carbone

  DOI：10.3390/molecules27010019

  日期：——

  effectively with the adenosine triphosphate binding pocket. Therefore, we assessed its ability to induce apoptosis (which increased 1.5- and 2-fold in PATU-T and PDAC3 cells, respectively) and to inhibit CDK1 expression, which was reduced to 45% in Hs766T. Lastly, compound 6b passed the ADME prediction, showing good pharmacokinetic parameters. These data demonstrate that 6b displays cytotoxic activity, induces

  胰腺导管腺癌 (PDAC) 是一种以耐药性为特征的高度致死性癌症，迫切需要新的治疗策略。近年来，蛋白激酶已成为治疗几种实体肿瘤和血液肿瘤的有希望的药理学靶标。有趣的是，细胞周期蛋白依赖性激酶 1 (CDK1) 在 PDAC 组织中过度表达，并且与这些肿瘤的侵袭性有关，因为它在细胞周期进程中的关键作用和对细胞凋亡诱导的抗性。由于这些原因，CDK1 是化学抗性的主要原因之一，代表了一个有前途的药理学靶点。在这项研究中，我们报告了新的 1,2,4-恶二唑化合物的合成，并评估了它们抑制 PATU-T、Hs766T 和 HPAF-II 细胞系和原代 PDAC 细胞培养物 (PDAC3) 细胞生长的能力。6b是最活跃的化合物，其 IC 50值范围为 5.7 至 10.7 µM。6b与 CDK1 活性位点的分子对接显示了该化合物与三磷酸腺苷结合袋有效相互作用的能力。因此，我们评估了其诱导细胞凋亡（在 PATU-T
• 5-HT.sub.4 receptor antagonists
  申请人：SmithKline Beecham p.l.c.

  公开号：US05492919A1

  公开（公告）日：1996-02-20

  The invention provides the use of a compound of formula (I) ##STR1## wherein A, E, F, U, X, Y, Z, are as defined in the specification, or a pharmaceutically acceptable salt thereof, for the treatment of diarrhea predominant irritable bowel syndrome.

  本发明提供了使用式(I)的化合物或其药学上可接受的盐，其中A、E、F、U、X、Y、Z如规范中所定义，用于治疗腹泻型肠易激综合症。
• OREXIN RECEPTOR ANTAGONISTS WHICH ARE [ORTHO BI-(HETERO-)ARYL]-[2-(META BI-(HETERO-)ARYL)-PYRROLIDIN-1-YL]-METHANONE DERIVATIVES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：US20150252032A1

  公开（公告）日：2015-09-10

  The present invention relates to [ortho bi-(hetero-)aryl]-[2-(meta bi-(hetero-)aryl)-pyrrolidin-1-yl]-methanone derivatives of formula (I) wherein R, and the rings A 1 A 2 and A 3 are as described in the description, to pharmaceutically acceptable salts thereof, to their preparation, to pharmaceutical compositions containing one or more compounds of formula (I), and to their use as pharmaceuticals, especially to their use as orexin receptor antagonists.

  本发明涉及公式（I）的[ortho bi-（hetero-）aryl]-[2-（meta bi-（hetero-）aryl）-pyrrolidin-1-yl]-methanone衍生物，其中R和环A1A2和A3如描述中所述，以及其药学上可接受的盐、其制备方法、含有一个或多个公式（I）化合物的制药组合物以及它们作为药物的用途，特别是作为促进睡眠激素受体拮抗剂的用途。
• Five-membered ring systems with bonded azacyclic ring substituents
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0328200A1

  公开（公告）日：1989-08-16

  The present invention provides a compound of formula I or a salt or prodrug thereof: wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: in which: R' represents hydrogen, hydroxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, hydroxy(C1-6)alkyl, halogen, amino, cyano, -CONR6R7 or -S02NR6R7, in which R6 and R7 independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; R2 represents hydrogen, halogen, C1 -6 alkyl, C1 -s alkoxy or C1 -6 alkylcarbonyl; V represents nitrogen, - CH or - C -; and W represents oxygen, sulphur or - NR8, in which R8 represents hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: . a) a non-aromatic azacyclic or azabicyclic ring system; or b) a group of formula -NRaRb, in which Ra and Rb independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-s alkynyl or aryl(C1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供了式 I 的化合物或其盐或原药： 其中圆点代表五元环任意位置上的一个或两个双键； X、Y和Z独立地代表氧、硫、氮或碳，条件是X、Y和Z中至少有一个代表氧、硫或氮； 其中 R'代表氢、羟基、C1-6 烷基、C2-6 烯基、C2-6 炔基、C1-6 烷氧基、羟基（C1-6）烷基、卤素、氨基、氰基、-CONR6R7 或 -S02NR6R7，其中 R6 和 R7 独立地代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； R2 代表氢、卤素、C1-6 烷基、C1-s 烷氧基或 C1-6 烷基羰基； V 代表氮、- CH 或 - C -；以及 W 代表氧、硫或- NR8，其中 R8 代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； E 代表键或含有 1 至 5 个碳原子的直链或支链亚烷基链，可选择被羟基或苯基取代； 以及 F 代表 a) 非芳氮杂环或氮杂环环系；或 b) 式-NRaRb 的基团，其中 Ra 和 Rb 独立代表氢、C1-6 烷基、C2-6 烯基、C2-s 烷炔基或芳基（C1-6）烷基。这些化合物可用于治疗精神病（如精神分裂症和躁狂症）、焦虑、戒酒或戒毒、疼痛、胃淤血、胃功能障碍（如消化不良、消化性溃疡、反流性食道炎和胀气）、偏头痛、恶心和呕吐以及先天性和老年性痴呆。